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    Lower KV7.5 Potassium Channel Subunit Expression in an Animal Model of Paroxysmal Dystonia (2016)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Sander, Svenja E (WE 14)
    Diwan, Mustansir
    Raymond, Roger
    Nobrega, José N
    Richter, Angelika
    Quelle
    CNS & neurological disorders drug targets; 15(1) — S. 95–101
    ISSN: 1996-3181
    Sprache
    Englisch
    Verweise
    Pubmed: 26553166
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    +49 30 838 53221
    pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Dystonia is a hyperkinetic disabling movement disorder. In the dt(sz) hamster, a model of paroxysmal dystonia, pronounced antidystonic effects of the KV7.2-5 potassium channel opener retigabine and aggravation of dystonia by a selective KV7.2-5 blocker indicated a pathophysiological role of an abnormal expression of KV7 channels. We therefore investigated the expression of KV7 subunits in brains of dystonic hamsters. While KV7.2 and KV7.3 subunits were unaltered, lower KV7.5 mRNA levels became evident in motor areas and in limbic structures of dystonic hamsters. The KV7.2/3 subunit-preferring channel opener N-(6-chloropyridin-3-yl)-3,4- difluorobenzamide (ICA 27243; 10-30 mg/kg i.p.) failed to reduce the severity of dystonia in mutant hamsters, suggesting that the previously observed antidystonic action of retigabine is mediated by the activation of KV7.5 channels. The experiments indicate a functional relevance for KV7.5 channels in paroxysmal dystonia. We suggest that compounds highly selective for subtypes of KV7 channels, i.e. for KV7.5, may provide new therapeutic approaches.